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Pancreatic Neoplasms: HELP
Articles by Marie-Nöelle Lavaut
Based on 6 articles published since 2010
(Why 6 articles?)
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Between 2010 and 2020, M-N Lavaut wrote the following 6 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
1 Article LIF Drives Neural Remodeling in Pancreatic Cancer and Offers a New Candidate Biomarker. 2018

Bressy, Christian / Lac, Sophie / Nigri, Jérémy / Leca, Julie / Roques, Julie / Lavaut, Marie-Nöelle / Secq, Véronique / Guillaumond, Fabienne / Bui, Thi-Thien / Pietrasz, Daniel / Granjeaud, Samuel / Bachet, Jean-Baptiste / Ouaissi, Mehdi / Iovanna, Juan / Vasseur, Sophie / Tomasini, Richard. ·CRCM, INSERM, U1068; Paoli-Calmettes Institute; Aix-Marseille University, UM 105; CNRS, UMR7258, Marseille, France. · Department of Pathology, Hospital North and Mediterranean University, Marseille, France. · INSERM UMRS 775, University PARIS DESCARTES, Paris, France. · Department of Hepatobiliary and Digestive Surgery, Groupe Hospitalier Pitié Salpêtrière, Paris, France. · Department of Hepatogastroentérology, Groupe Hospitalier Pitié Salpêtrière, Paris, France. · Aix-Marseille University, INSERM, CRO2, UMR 911, Marseille, France. · CRCM, INSERM, U1068; Paoli-Calmettes Institute; Aix-Marseille University, UM 105; CNRS, UMR7258, Marseille, France. richard.tomasini@inserm.fr. ·Cancer Res · Pubmed #29269518.

ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) is characterized by extensive stroma and pathogenic modifications to the peripheral nervous system that elevate metastatic capacity. In this study, we show that the IL6-related stem cell-promoting factor LIF supports PDAC-associated neural remodeling (PANR). LIF was overexpressed in tumor tissue compared with healthy pancreas, but its receptors LIFR and gp130 were expressed only in intratumoral nerves. Cancer cells and stromal cells in PDAC tissues both expressed LIF, but only stromal cells could secrete it. Biological investigations showed that LIF promoted the differentiation of glial nerve sheath Schwann cells and induced their migration by activating JAK/STAT3/AKT signaling. LIF also induced neuronal plasticity in dorsal root ganglia neurons by increasing the number of neurites and the soma area. Notably, injection of LIF-blocking antibody into PDAC-bearing mice reduced intratumoral nerve density, supporting a critical role for LIF function in PANR. In serum from human PDAC patients and mouse models of PDAC, we found that LIF titers positively correlated with intratumoral nerve density. Taken together, our findings suggest LIF as a candidate serum biomarker and diagnostic tool and a possible therapeutic target for limiting the impact of PANR in PDAC pathophysiology and metastatic progression.

2 Article Collagen-derived proline promotes pancreatic ductal adenocarcinoma cell survival under nutrient limited conditions. 2017

Olivares, Orianne / Mayers, Jared R / Gouirand, Victoire / Torrence, Margaret E / Gicquel, Tristan / Borge, Laurence / Lac, Sophie / Roques, Julie / Lavaut, Marie-Noëlle / Berthezène, Patrice / Rubis, Marion / Secq, Veronique / Garcia, Stéphane / Moutardier, Vincent / Lombardo, Dominique / Iovanna, Juan Lucio / Tomasini, Richard / Guillaumond, Fabienne / Vander Heiden, Matthew G / Vasseur, Sophie. ·Centre de Recherche en Cancérologie de Marseille (CRCM), Unité 1068, Institut National de la Santé et de la Recherche Médicale, Marseille F-13009, France. · Institut Paoli-Calmettes (IPC), Marseille F-13009, France. · Unité Mixte de Recherche (UMR 7258), Centre National de la Recherche Scientifique (CNRS), Marseille F-13009, France. · Université Aix-Marseille, Marseille F-13284, France. · Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Garscube Estate, Switchback Road, Bearsden, Glasgow G61 1QH, UK. · Koch Institute for Integrative Cancer Research and Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA. · Aix Marseille Univ, INSERM, CRO2, Marseille F-13005, France. · Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA. ·Nat Commun · Pubmed #28685754.

ABSTRACT: Tissue architecture contributes to pancreatic ductal adenocarcinoma (PDAC) phenotypes. Cancer cells within PDAC form gland-like structures embedded in a collagen-rich meshwork where nutrients and oxygen are scarce. Altered metabolism is needed for tumour cells to survive in this environment, but the metabolic modifications that allow PDAC cells to endure these conditions are incompletely understood. Here we demonstrate that collagen serves as a proline reservoir for PDAC cells to use as a nutrient source when other fuels are limited. We show PDAC cells are able to take up collagen fragments, which can promote PDAC cell survival under nutrient limited conditions, and that collagen-derived proline contributes to PDAC cell metabolism. Finally, we show that proline oxidase (PRODH1) is required for PDAC cell proliferation in vitro and in vivo. Collectively, our results indicate that PDAC extracellular matrix represents a nutrient reservoir for tumour cells highlighting the metabolic flexibility of this cancer.

3 Article Cancer-associated fibroblast-derived annexin A6+ extracellular vesicles support pancreatic cancer aggressiveness. 2016

Leca, Julie / Martinez, Sébastien / Lac, Sophie / Nigri, Jérémy / Secq, Véronique / Rubis, Marion / Bressy, Christian / Sergé, Arnauld / Lavaut, Marie-Noelle / Dusetti, Nelson / Loncle, Céline / Roques, Julie / Pietrasz, Daniel / Bousquet, Corinne / Garcia, Stéphane / Granjeaud, Samuel / Ouaissi, Mehdi / Bachet, Jean Baptiste / Brun, Christine / Iovanna, Juan L / Zimmermann, Pascale / Vasseur, Sophie / Tomasini, Richard. · ·J Clin Invest · Pubmed #27701147.

ABSTRACT: The intratumoral microenvironment, or stroma, is of major importance in the pathobiology of pancreatic ductal adenocarcinoma (PDA), and specific conditions in the stroma may promote increased cancer aggressiveness. We hypothesized that this heterogeneous and evolving compartment drastically influences tumor cell abilities, which in turn influences PDA aggressiveness through crosstalk that is mediated by extracellular vesicles (EVs). Here, we have analyzed the PDA proteomic stromal signature and identified a contribution of the annexin A6/LDL receptor-related protein 1/thrombospondin 1 (ANXA6/LRP1/TSP1) complex in tumor cell crosstalk. Formation of the ANXA6/LRP1/TSP1 complex was restricted to cancer-associated fibroblasts (CAFs) and required physiopathologic culture conditions that improved tumor cell survival and migration. Increased PDA aggressiveness was dependent on tumor cell-mediated uptake of CAF-derived ANXA6+ EVs carrying the ANXA6/LRP1/TSP1 complex. Depletion of ANXA6 in CAFs impaired complex formation and subsequently impaired PDA and metastasis occurrence, while injection of CAF-derived ANXA6+ EVs enhanced tumorigenesis. We found that the presence of ANXA6+ EVs in serum was restricted to PDA patients and represents a potential biomarker for PDA grade. These findings suggest that CAF-tumor cell crosstalk supported by ANXA6+ EVs is predictive of PDA aggressiveness, highlighting a therapeutic target and potential biomarker for PDA.

4 Article Cholesterol uptake disruption, in association with chemotherapy, is a promising combined metabolic therapy for pancreatic adenocarcinoma. 2015

Guillaumond, Fabienne / Bidaut, Ghislain / Ouaissi, Mehdi / Servais, Stéphane / Gouirand, Victoire / Olivares, Orianne / Lac, Sophie / Borge, Laurence / Roques, Julie / Gayet, Odile / Pinault, Michelle / Guimaraes, Cyrille / Nigri, Jérémy / Loncle, Céline / Lavaut, Marie-Noëlle / Garcia, Stéphane / Tailleux, Anne / Staels, Bart / Calvo, Ezequiel / Tomasini, Richard / Iovanna, Juan Lucio / Vasseur, Sophie. ·INSERM, U1068, Centre de Recherche en Cancérologie de Marseille, Institut Paoli-Calmettes, CNRS, UMR7258, and Université Aix-Marseille, F-13009 Marseille, France; · INSERM, UMR911, Centre de Recherche en Oncologie Biologique et Oncopharmacologie, F-13385 Marseille, France; Service de Chirurgie Digestive et Viscérale, F-13385 Marseille, France; · INSERM, U1069, Laboratoire Nutrition, Croissance et Cancer, Université François Rabelais, F-37032 Tours, France; · INSERM, U1068, Centre de Recherche en Cancérologie de Marseille, Institut Paoli-Calmettes, CNRS, UMR7258, and Université Aix-Marseille, F-13009 Marseille, France; Service Hospitalier d'Anatomie et Cytologie Pathologiques Humaines, Assistance Publique-Hôpitaux de Marseille, F-13015 Marseille, France; · European Genomic Institute for Diabetes, FR 3508, Université Lille 2, INSERM, U1011, and Institut Pasteur de Lille, F-59019 Lille, France; and. · Molecular Endocrinology and Oncology Research Center, Quebec, QC, Canada G1V 4G2. · INSERM, U1068, Centre de Recherche en Cancérologie de Marseille, Institut Paoli-Calmettes, CNRS, UMR7258, and Université Aix-Marseille, F-13009 Marseille, France; sophie.vasseur@inserm.fr. ·Proc Natl Acad Sci U S A · Pubmed #25675507.

ABSTRACT: The malignant progression of pancreatic ductal adenocarcinoma (PDAC) is accompanied by a profound desmoplasia, which forces proliferating tumor cells to metabolically adapt to this new microenvironment. We established the PDAC metabolic signature to highlight the main activated tumor metabolic pathways. Comparative transcriptomic analysis identified lipid-related metabolic pathways as being the most highly enriched in PDAC, compared with a normal pancreas. Our study revealed that lipoprotein metabolic processes, in particular cholesterol uptake, are drastically activated in the tumor. This process results in an increase in the amount of cholesterol and an overexpression of the low-density lipoprotein receptor (LDLR) in pancreatic tumor cells. These findings identify LDLR as a novel metabolic target to limit PDAC progression. Here, we demonstrate that shRNA silencing of LDLR, in pancreatic tumor cells, profoundly reduces uptake of cholesterol and alters its distribution, decreases tumor cell proliferation, and limits activation of ERK1/2 survival pathway. Moreover, blocking cholesterol uptake sensitizes cells to chemotherapeutic drugs and potentiates the effect of chemotherapy on PDAC regression. Clinically, high PDAC Ldlr expression is not restricted to a specific tumor stage but is correlated to a higher risk of disease recurrence. This study provides a precise overview of lipid metabolic pathways that are disturbed in PDAC. We also highlight the high dependence of pancreatic cancer cells upon cholesterol uptake, and identify LDLR as a promising metabolic target for combined therapy, to limit PDAC progression and disease patient relapse.

5 Article Stromal SLIT2 impacts on pancreatic cancer-associated neural remodeling. 2015

Secq, V / Leca, J / Bressy, C / Guillaumond, F / Skrobuk, P / Nigri, J / Lac, S / Lavaut, M-N / Bui, T-T / Thakur, A K / Callizot, N / Steinschneider, R / Berthezene, P / Dusetti, N / Ouaissi, M / Moutardier, V / Calvo, E / Bousquet, C / Garcia, S / Bidaut, G / Vasseur, S / Iovanna, J L / Tomasini, R. ·1] CRCM, Cellular Stress, INSERM, U1068, Parc scientifique de Luminy, Paoli-Calmettes Institute, Aix-Marseille University, UM 105, CNRS, UMR7258, Marseille 13009, France [2] Department of Pathology, Hospital North/Mediterranean University, Marseille, France. · CRCM, Cellular Stress, INSERM, U1068, Parc scientifique de Luminy, Paoli-Calmettes Institute, Aix-Marseille University, UM 105, CNRS, UMR7258, Marseille 13009, France. · Neuronexperts, Medical North Faculty, Marseille, France. · Aix-Marseille University, INSERM, CRO2, UMR 911, Marseille 13385, France. · Molecular Endocrinology and Oncology Research Center, CHUL Research Center, Quebec City, QCue, Canada. · INSERM UMR 1037, CRCT, University Toulouse III, Toulouse, France. ·Cell Death Dis · Pubmed #25590802.

ABSTRACT: Pancreatic ductal adenocarcinoma (PDA) is a critical health issue in the field of cancer, with few therapeutic options. Evidence supports an implication of the intratumoral microenvironment (stroma) on PDA progression. However, its contribution to the role of neuroplastic changes within the pathophysiology and clinical course of PDA, through tumor recurrence and neuropathic pain, remains unknown, neglecting a putative, therapeutic window. Here, we report that the intratumoral microenvironment is a mediator of PDA-associated neural remodeling (PANR), and we highlight factors such as 'SLIT2' (an axon guidance molecule), which is expressed by cancer-associated fibroblasts (CAFs), that impact on neuroplastic changes in human PDA. We showed that 'CAF-secreted SLIT2' increases neurite outgrowth from dorsal root ganglia neurons as well as from Schwann cell migration/proliferation by modulating N-cadherin/β-catenin signaling. Importantly, SLIT2/ROBO signaling inhibition disrupts this stromal/neural connection. Finally, we revealed that SLIT2 expression and CAFs are correlated with neural remodeling within human and mouse PDA. All together, our data demonstrate the implication of CAFs, through the secretion of axon guidance molecule, in PANR. Furthermore, it provides rationale to investigate the disruption of the stromal/neural compartment connection with SLIT2/ROBO inhibitors for the treatment of pancreatic cancer recurrence and pain.

6 Article Strengthened glycolysis under hypoxia supports tumor symbiosis and hexosamine biosynthesis in pancreatic adenocarcinoma. 2013

Guillaumond, Fabienne / Leca, Julie / Olivares, Orianne / Lavaut, Marie-Noëlle / Vidal, Nicolas / Berthezène, Patrice / Dusetti, Nelson Javier / Loncle, Céline / Calvo, Ezequiel / Turrini, Olivier / Iovanna, Juan Lucio / Tomasini, Richard / Vasseur, Sophie. ·Centre de Recherche en Cancérologie de Marseille (CRCM), Unité 1068, Institut National de la Santé et de la Recherche Médicale, F-13009 Marseille, France. ·Proc Natl Acad Sci U S A · Pubmed #23407165.

ABSTRACT: Pancreatic ductal adenocarcinoma is one of the most intractable and fatal cancer. The decreased blood vessel density displayed by this tumor not only favors its resistance to chemotherapy but also participates in its aggressiveness due to the consequent high degree of hypoxia. It is indeed clear that hypoxia promotes selective pressure on malignant cells that must develop adaptive metabolic responses to reach their energetic and biosynthetic demands. Here, using a well-defined mouse model of pancreatic cancer, we report that hypoxic areas from pancreatic ductal adenocarcinoma are mainly composed of epithelial cells harboring epithelial-mesenchymal transition features and expressing glycolytic markers, two characteristics associated with tumor aggressiveness. We also show that hypoxia increases the "glycolytic" switch of pancreatic cancer cells from oxydative phosphorylation to lactate production and we demonstrate that increased lactate efflux from hypoxic cancer cells favors the growth of normoxic cancer cells. In addition, we show that glutamine metabolization by hypoxic pancreatic tumor cells is necessary for their survival. Metabolized glucose and glutamine converge toward a common pathway, termed hexosamine biosynthetic pathway, which allows O-linked N-acetylglucosamine modifications of proteins. Here, we report that hypoxia increases transcription of hexosamine biosynthetic pathway genes as well as levels of O-glycosylated proteins and that O-linked N-acetylglucosaminylation of proteins is a process required for hypoxic pancreatic cancer cell survival. Our results demonstrate that hypoxia-driven metabolic adaptive processes, such as high glycolytic rate and hexosamine biosynthetic pathway activation, favor hypoxic and normoxic cancer cell survival and correlate with pancreatic ductal adenocarcinoma aggressiveness.